Automatic pipette



April 5, 1966 Filed Aug. 22, 1963 H. G. TIETJE ETAL 3,244,009

AUTOMATIC PIPETTE 5 Sheets-Sheet 1 u w a I a I I //a a? r i INVENTORS ATTO/PA EYJ April 5, 1966 H. ca. TIETJE ETAL AUTOMATIC PIPETTE Filed Aug. 22, 1963 5 Sheets-Sheet 2 ATTORNEYS April 5, 1966 H. G. TIETJE ETAL AUTOMATIC PIPETTE 5 Sheets-Sheet 5 Filed Aug. 22, 1963 INVENTORS HEA M07 4. 7757775 K08 Eff SCHWAEZ, JR. Y

ATTUK/VFVS United States Patent 3,244,009 AUTOMATIC PlPETT E Helrnut G. Tietje, Westwood, and Robert Schwarz, Jr.,

Tenafly, N.J., assignors to Becton, Dickinson & Company, East Rutherford, NJ., a corporation of New Jersey Filed Aug. 22, 1963, Ser. No. 303,798 20 Claims. (Cl. 73--425.6)

This invention relates to certain improvements in automatic pipettes and in particular to pipettes of this nature having the added advantage of being capable of influencing the operation of timing devices.

An exact amount of fluid is oftentimes required to be pipetted in microchemistry or other biological or chemical applications. This pipetting is frequently employed in conjunction with time measurements as, for example, the determination of reaction times. Many other tests require accurate timing. Heretofore, the timing was usually started with a stop watch when a particular material was pipetted into another. The exact time of reaction was then clocked.

Although the present invention has wider applications in thefield of biology, chemistry, medicine and related sciences, the present discussion will be devoted primarily to certain clinical and laboratory procedures, specifically,

prothrombin and coagulation time determinations. It should be understood, however, that this invention is not intended to be limited thereby and contemplates these as well as other applications. Accordingly, in clinical as well as laboratory practice, samples of materials to be tested are frequently placed in tubes, vials or similar vessels and receptacles. In this connection, various controls and reagents are similarly contained as part of the diagnosis and therapy under consideration. The particular tube contents may then be placed throng-h at least one of a series of tests or may even have samples extracted or aspirated as part of the test procedure.

In prothrombin and coagulation time determinations, standardized and stabilized chemical reagents are placed in tubes and heated to selected operating temperatures, approximately that of the normal human body. The quantity of reagent is ordinarily fixed for proper time determinations. Control plasma of predetermined quantity, also in such tubes, is then dispensed in one of the tubes containing a reagent. A probe, either manually or automatically operated is then inserted and withdrawn from the tube for purposes of sensing the initial clot formation. Apparatus capable of such performance is disclosed in patent application SN. 188,934 filed April 18, 1962. The same procedure is then followed utilizing a controlled amount of patients plasma. The prothrombin times are read and recorded.

It should now be clear that the volumetric control of the liquids as well as the exact moment at which the time measurement is commenced are important factors effecting the accuracy and reproducibility of the test together with results. As will be explained, the present invention proposes optimizing these volumetric and timing controls for arriving at a high standard of testing results and reproducibility.

The present invention has, as one of its principal objects, the provisions of a pipetting device adapted to send a signal to such mechanisms as timing motors or digital readouts at the exact time of expulsion of the fluid from a pipette tip in order to more accurately initiate the commencement of the cycle of measurement.

Another object is to provide an improved automatic pipette having a disposable tip and capable of pipetting minute quantities of liquids rapidly and accurately thereby providing for optimum reproducibility of measurements.

3,244,009 Patented Apr. 5, 1966 A further object is to provide an automatic pipette having replaceable tips which minimize, if not eliminate, the need for cleaning following each pipetting operation; and, in addition, a pipette fabricated from a minimum number of parts each individually simple and easy to manufacture and readily assembled at a minimum of cost to form a device manipulated rather efliciently and without skill.

A pipette fabricated in accordance with this invention includes a casing having a substantially tapered barrel with a handle extending transversely therefrom. A removable tube is at one end of the barrel whereas a longitudinally displaceable plunger is at the other end. This plunger mounts a piston operable wit-bin the bore of the tube. The plunger and, consequently, the piston is biased outwardly by means of a return spring.

A coupling is adapted to be detachably mounted on the free end of the barrel and serves to couple a disposable pipette tip in such a manner that the lumen of the tip and the bore of the tube are in communication with one another. Under these circumstances, all liquid will only be contained within the passageway of the tip and at no time is any liquid intended to be withdrawn into the bore of the tube. Thus, upon retraction of the plunger, a cerain amount of liquid will be drawn into the tip. By the same token, upon movement of the piston forwardly, liquid will be dispensed therefrom,

A contemplated application of the automatic pipette of this invention is to initiate the operation of a coagulation timer of the type disclosed in the above referenced application S.N. 188,934, filed April 18, 1962, simultaneously with the ejection of liquid from the tip. Accordingly, electrical contacts within the handle are adapted to be closed upon the depression of the plunger. In this connection, the plunger may be suitably slotted for receiving extensions of these contacts for controlling the amount of liquid ejected from the tip. Under these circumstances, the plunger will only be permitted a certain displacement with respect to the barrel corresponding to a certain quantity of liquid to be dispensed which, in accordance with contemplated embodiments, will be in the order of .1 or .2 ml. or larger, if desired. The plunger is rotatable relative to the casing to permit the selected slot to be aligned with the free ends of the contacts. When the plunger is depressed, the wall of the selected slot will eventually close the switch contacts immediately following the dispensing of the predetermined volume or amount of liquid. I

A safety switch is incorporated into the pipette and serves to prevent accidental closing of the circuit containing the above switch contacts to thereby guard against premature actuation of the timer. An electrical jack conveniently interconnects the timer with the pipette, it being understood that the pipette of this invention has application other than in conjunction with a timer and quite independently thereof.

Other objects and advantages will become apparent from the following detailed description which is to be taken in conjunction with the accompanying drawings illustrating a somewhat preferred embodiment of the invention and in which:

FIG. 1 is a reduced perspective view of the automatic pipette associated with an electrical connection coupling with a timer, the disposable tip being shown in operative relationship with respect to a tube or vial for containing the reaction mixture;

FIG. 2 is an enlarged longitudinal sectional view taken along the line 22 of FIG. 1 with certain parts broken away and removed for clarity;

FIG. 3 is a similar view with the safety switch closed and the plunger depressed with resultant expelling of liquid from the tip;

FIG. 4 is a cross sectional view taken along the line 44 of FIG. 2;

FIG. 5 is a somewhat enlarged cross sectional view taken along the line 55 of FIG. 3;

FIG. 6 is a top plan view of the pipette broken away and sectioned as shown to reveal the upper interior of the casing;

FIG. 7 is a sectional view taken along the line 7-7 of FIG. 2 showing the interior of the handle;

-FIG. 8 is an enlarged longitudinal sectional view of disposable pipette tip contemplated by this invention; and

FIG. 9 is a fragmentary view showing the rear of the plunger in elevation together with the associated parts of the pipette casing.

In the drawings, a pipette 2%) is shown capable of accomplishing the intended purposes. This pipette comprises a plunger 22 reciprocal in a casing which includes a forwardly disposed tubular barrel 24 from which extends a transverse integral handle 26, the rear ending of which is closed by end panel 28. The forward end of the tubular barrel 24 is formed with a coaxial substantially inwardly extending cylinder as well as a forwardly extending split or slotted conical boss 32 provided with an interrupted periphery extending outer latching lip 34. The embraced interior 36 of the boss defines with bore 38 of the cylinder 30 a circumferentially extending shoulder 40. The interior of the barrel 24 is formed with a number of inwardly extending flanges including a pair of upper and lower stop flanges 42 and 44. These specific flanges prevent rotation of the piston and plunger 22 when in an inserted position within the barrel; and they prevent forward movement when the plunger is in a retracted position but improperly oriented for the desired dosage.

Two other sets of guiding flanges 46 and 48 extending from the sides of the barrel 24. In addition, stop flanges 50 are disposed between the guide flanges 46 and serve to limit the forward stroke of the plunger 22 in accordance with a preselected dosage to be pipetted upon execution of a particular stroke. Stop flanges 52 are disposed between the guide flanges 48 and are somewhat longer in length than the stop flanges 50 in order to provide for reduced amount of permissable forward movement of the plunger 22 and, consequently, dosage pipetted.

The handle 26 is provided with a pair of bored studs 54 and 56 which serve to threadedly receive the mounting screws 58 and 60, respectively, for the rear panel 28. In addition, a pair of bored studs 62 and 64 cooperate with the studs 54 and 56 in mounting electrical contacts 66, 68 and 78, as shown. These contacts are suitably guided and maintained in their operative position by means of the network of internal ribs generally designated by the numeral 72 appearing on both sides of the internal face and the handle 26. The lower end of the handle 26 is provided with an upwardly extending opening 74 which receives the pronged end 76 of the jack 78 in completing the electrical connection between the handle switches and the timer 80.

The rear cover plate 28 is provided with countersunk openings 82 and 84 for receiving the head of the respective screws 58 and 60. This cover plate is also provided with a centrally somewhat elongated rectangular open- 7 ing 86 that permits vertically reciprocalmovement of the switch button 88. This button is possessed with a roughened finger engaging projection surface 90 extending outwardly from the cover plate 28 and an inner bevelled or cammed surface 92 in engagement with the normally opened switch contact 78. The bevelled surface 92 is provided with a pair of spaced grooves or recesses 94 and 96 which serve to determine, respectively, the open position and closed position of the contact 70. In this connection, the closed position will result in the engagement of the contact 70 with the contact 68 which, in turn, is normally opened with respect to the third contact 66. In regard to the latter contacts 66 and 68, they are adapted to be 4 closed upon actuation of the plunger 22 in a forwardly direction.

The rear cover plate is additionally provided with a substantially circular opening 98 through which the plunger 22 is adapted to reciprocate. An integral inwardly extending substantially circular guide 100 serves tomaintain the plunger 22 in the desired coaxial relationship with respect to the barrel 24. during the forward stroke as well as retractiton of the plunger. In addition, it acts as a stop for the plunger. As will be appreciated, the base of the circular guide 100 is formed with a recess 192 which conveniently accommodates the free end of the switch contacts 66 and 68 which are adapted to be closed upon engagement with surfaces of the plunger 22 in a manner to be explored in detail shortly.

The upper end of the rear cover plate 2 8 is provided with a finger grip 104 which facilitates the manipulation of the plunger 22 and dispensing of the pipette contents. The base of the finger grip 104 is adapted to engage an upwardly extending lip 106 on the tubular barrel 24 and thereby prevent movement of the grip 104 relative to the barrel 24 as the plunger is depressed.

Referring now to the plunger 22, it will be observed that its rear end fixedly mounts a finger engaging button 198 which conveniently includes indicia indicating the dosage obtained upon depression of the plunger 22 in accordance with the setting of the plunger and its particular orientation relative to the barrel 24. In this connection, and in accordance with a successful specific application and embodiment of the invention, the button 108is' provided with a notch or groove 110 to indicatea setting of the plunger which will afford dispensing of .1 mm. of fluid; whereas the diametrically opposed part of the button 108 may include two of such notches 112 which would indicate a .2 mm. setting. The forward end of the plunger 22 is provided with a laterally extending integral plate or flange 114 which serves as a key for cooperating with the internal flanges of the barrel 24 in obtaining accurate dispensing of liquid amounts. As will be explained, this plate 114, when oriented in accordance with the desired dosage setting, will ultimately engage with the stop flanges 50 and 52.

The plunger 22 is provided with a pair of opposed slots 116 and 118 which permits free travel therethrough of the terminal ends of the electrical contacts 66 and 68 but' when the end of the accommodating slot is reached, the contacts will be forced into the closed position. In this connection, a slot will be selected in accordance with the desired setting as indicated by the indicia appearing on the plunger button 108 which, in turn, is determined by' the quantity of liquid to be dispensed. Under these circumstances, the laterally projecting plate 114 will be so oriented within the tubular barrel 24 for this measured quantity of liquid that will either engage the stop flanges 50' or 52. As previously explained, when the setting has been executed and the plunger 22 then depressed, the predetermined quantity of liquid is pipetted. immediately upon completion of this sequence of events, the switch contacts 66 and 68 will be closed by the end of the particular accommodating slot 116 or 118 to thereby actuate the connected timer.

The forward end of the plunger 22 is provided with a rod extension 126 suitably secured thereto as, forexample, by means of the illustrated wedge-shaped serrations appearing at the inner rod end 122 engaging with the surfaces defining the inner bore 124 of the plunger. On the other hand, this rod may be an integral extension of the plunger. The outer or distal end of the extension rod is suitably grooved for accommodating the O-ring 126 which rides or travels in the removable tube 128 partially disposed in the bore 38. v

The plunger together with its rod extension 120 is biased rearwardly by means of the compression spring 130 which has one end thereof engaged against the forward end of the barrel 24 while embracing the exterior at this location.

of the inwardly extending cylinder 30, while the other end is in engagement with the radial flange 113 from which the plate 114 extends.

A coupling 132 is releasably latched to the forward end of the barrel 24 and serves to associate a disposable pipette tip 134 thereto and to the plunger action. Thus, the coupling 132 is provided with a bore 136 which receives the forward end of the tube 128. A reduced bore 138 cooperates with the bore 136 in defining shoulder 48 against which the forward end of the tube rests. In this connection, a tube 128 may be suitably secured to the coupling 132 as, for example, by welding. The coupling is provided with an inner conical face 142 which mates with the exterior of the conical boss 32. In addition, a circumferentially extending groove 144 is also provided for receiving the lip 34 at the forward end of the barrel 24. As will be apparent in coupling the parts together, the conical surface 142 acts as a wedge against the lip 34 and cams the lip radially inwardly as a result of the longitudinally extending slots in the boss 32 until such time as the lip is permitted to shift radially outwardly into the groove 144. The coupling will be, accordingly, releasably latched to the forward end of the barrel 24. The proper orientation of the coupling with respect to the barrel will be obtained by means of the key and keyway assembly 146 provided by the mating surfaces of the coupling and boss.

The forward end of the coupling 132 is formed with a downwardly or obliquely extending conically shaped bore 148 communicating with a reduced bore 138. This bore serves to receive by means of a wedge friction fit, a mating and correspondingly shaped rear end 150 of the pipette tip 134.

Referring now to the disposal tip 134, it should be understood that a precision engineered element is contemplated whereby no liquid hang up is experienced upon pipetting. An inner tapered or conically shaped bore 152 is formal in the pipette and is of relatively small diameter throughout for such purposes. In addition, the tapered leading end 154 of the pipette contributes to the minimization of tendency for liquid to hang up. The elongated nature and extended length of the pipette in relation to the inner diameter not only provides the necessary capacity for the pipette but permits a rather smooth taper from the large to smaller diameter tip thereby reducing the tendency of liquid to surge at the tip during or as a result of the dispensing operation. The sharper the angle at the tip 154 together with the minimization of the exterior surface area at the terminal end of the tip also eliminates the tendency of a bubble to hang up A series of ribs 156 at the hub of the disposable tip 134 facilitates twisting and pushing of the hub 150 into the bore 143 of the coupling 132. A rather small orifice pipette tip is selected eliminate any loss of liquid when liquid is withdrawn into the bore 152 of the tip; A vacuum head thereby exists above the liquid column in the pipette tip which holds the liquid in the tip. In this connection, also, liquid surface tension contributes to the maintenance of liquid in the tip. By the same token, once liquid is withdrawn in the tip, the entrapped air which would have a piston effect on the liquid during dispensing, should not be permitted to escape. In other words, optimum piston action during intake and dispensing is preferred. Accordingly, accurate and volumetric control is contemplated by this invention with the dimensional properties and characteristics including the relatively long and thin configuration of the tip contributing to this desired end result.

A successful disposable tip 134 included the following dimensional characteristic:

Overall length in 3.33 Wall thickness in .025 Angle of taper deg 154-60 Internal diameter at forward end in .040

6 Internal diameter at rear end in .140 Capacity at 2.48 inch level from forward end ml .205

Although a number of materials can be satisfactorily employed in conjunction with the fabrication of the various parts constituting the pipette of this invention, satisfactory and successful applications as well as results have been experienced with the following selection. A dimensional stable metal was utilized for the tube 128 and coupling 132 particularly for optimum reproducibility of pipetting results. The tip was either formed from styrene or polyethylene. Any other nonwettable plastic of a transparent nature could be employed for assuring liquid withdrawal. For the tubular barrel 24 and integrally extending handle 26, rear cover plate 28, plunger 22 and the other moldable resin parts, commercially available Delrin supplied 'by E. I. duPont de Nemours & Co. 1110., Wilmington 98, Delaware, was successfully utilized. This particular material has relatively high fatigue resistant characteristics as well as optimum dimensional tolerances with minimum temperature effects.

Summarizing the operation of the automatic pipette of this invention and assuming that the pipette 20 is coupled with a timer by means of the electrical jack 76, the piston 22 is rotated relative to the barrel 24 to the selected volumetric increment indicated by means of the indicia on the plunger button 108 for the dosage of liquid to be dispensed. The switch button 88 should be shifted to its off position. A fresh disposable tip 134 should be mounted in the coupling 132 appearing at the forward end of the barrel 24. The plunger 22 is depressed or shifted forwardly; and the tip 134 is then placed in or immersed in the liquid to be pipetted. In the case of prothrombin time determinations, this liquid would be plasma, and after the tip 134 has been inserted into the liquid, the plunger 22 is retracted to aspirate the selected dosage of plasma into the bore or lumen 152 of the tip 134. Upon completion of aspiration, the flange plate 114 will be in engagement with the circular member now functioning as a stop or limiting means 100. An accurate quantity of volume of the plasma will, accordingly, be withdrawn in the tip 152 with a column of air separating the forward end of the plunger extension rod and the plasma servin as a pneumatic head in re taining the plasma in the tip through the cooperation of the surface tension of the liquid. The tip 134 is then withdrawn from the plasma and the switch button 88 shifted to the on position or at which the contact 70 will close with the contact 68. The accurate amount of plasma will now be expelled into a reaction well including the desired quantity of reaction substance by shifting the plunger 22 forwardly. Under these circumstances, the entrapped air forwardly of the O-ring 126 will act upon the upper surface of the plasma in the tip 134 and pipette it outwardly through the tapered end 154. At the completion of the forward stroke of the plunger 22, the end of the slot 116 or 118, depending upon the dosage selected, will cause the contacts 66 and 68 to close thereby completing the electrical circuit to the timer 80 which will now be set into operation to determine the time of sensing of the initial clot formation and, consequently, the prothrombin time.

It will be found by those skilled in the art that the accuracy and reproducibility of the pipette exceed by a considerable margin the capabilities of the average laboratory technician using conventional glass pipettes. Pipettes incorporating the teachings of this invention have a mean absolute accuracy of less than 2 percent of the indicated volume. Reproducibility on any given pipette is in the order of :2 percent. The provisions for simultaneous starting of a timer insures accurate timing of the reaction and completely eliminates any variation which may result from the operation of the timer by several technicians. Cleansin problems are also eliminated be- 7 cause fluid never enters the body'of the pipette and the tips are disposable.

Thus, among others, the numerous aforenoted objects and advantages are most effectively attained. Although a single somewhat preferred embodiment of the invention has been disclosed and described in detail herein, it should be understood that this invention is in no sense limited thereby but its scope is to be determined by that of the appended claims.

We claim:

1. An automatic pipette comprising a barrel, a piston reciprocal forwardly and rearwardly therein, a disposable 'tip, coupling means for interconnecting said tip with the forward end of said barrel, whereby upon retraction rearwardly of said piston relative to said barrel, liquid is adapted to be drawn into said tip short of said barrel with a body of air being disposed intermediate the piston and the liquid in said tip and upon forward movement of the piston, the interposed air will act on the liquid to dispense'the liquid from the tip, said coupling means being so constructed and arranged such that the longitudinal axis of'said tip is disposed at an acute angle with respect to'the axis of said barrel, and key means provided by surfaces of said coupling means and the forward end of said barrel for assuring a predetermined disposition of the coupling means relative to said barrel.

2. The invention in accordance with claim 1 wherein releasable latch means is provided by surfaces of said coupling means and the forward end of said barrel for releasably latching the coupling means to the forward "end of said barrel.

3. The invention in accordance with claim 1 wherein key means are provided by surfaces of said coupling means and the forward end of said barrel for assuring a predetermined disposition of the coupling means relative to said barrel.

4. The invention in accordance with claim 1 wherein said coupling means and tube are welded to one another.

5. An automatic pipette comprising a barrel, a piston reciprocal forwardly and rearwardly therein, means for removably coupling a pipete tip with said barrel such that upon retraction rearwardly of said piston relative to said barrel, liquid is adapted to be drawn into said tip short of said barrel with a body of air being disposed intermediate the piston and the liquid in said tip and upon forward movement of the piston, the interposed air will act on the liquid to dispense the liquid from the tip, releasable latch means being provided by surfaces of the coupling means and the forward end of said barrel for releasably latchin the coupling means to the forward end of said barrel, key means being provided by surfaces of said coupling means and the forward end of said barrel for'assuring a predetermined disposition of the coupling means relative to said barrel, said piston being relatively rotatable with respect to said barrel, and dosage regulating means provided by surfaces of said piston and said barrel such that upon selective rotation of the plunger relative to said barrel, said plunger is provided with a predetermined stroke relative to said barrel and, consequently,

the amount of liquid withdrawn into and dispensed from the tip is regulated, said dosage regulating means including projecting stop and guide flanges on the interior of said barrel and a laterally extending flange being on interior surfaces of said plunger whereby upon predeter- 8 and plunger to normally urge said plunger out of the barrel.

7. The invention in accordance with claim 5 wherein switch means are coupled with said plunger and adapted to be actuated by the reciprocation thereof whereby a signal is adapted to be generated when said plunger assumes a predetermined position relative to the barrel at which a predetermined dosage of liquid is also dispensed from the tip.

'8. The invention in accordance with claim 5 wherein said plunger includes indicia means for setting the plunger relative to the barrel in selecting a predetermined dosage of liquid to be dispensed.

'9. An automatic pipette comprising a barrel, a'plunger reciprocally forwardly and rearwardly therein, means for coupling a tip to said barrel such that upon retraction rearwardly of said piston relative to said barrel, liquid is adapted to be drawn into said tip short of said barrel with a body of air being disposed intermediate the piston and the liquid in said tip and upon forward movementof the piston, the interposed air will'act on the liquid to dispense the liquid from the tip, and switch means coupled with said'plunger and being adapted to be actuated upon disposition of said plunger in a predetermined position relative to. said barrel to thereby permit asignaltobe sent upon assumption of this predetermined position of the plunger relative to the barrel.

10. The invention in accordance with claim 9 further including dosage regulating means including projecting stopand guide flanges on the interior of said barrel and a laterally extending flange on interior surfaces of said plunger whereby upon predetermined rotationof said plunger when fully withdrawn relative to the barrel and have its movement limited by a stop flange 'tothereby impart a predetermined stroke to the plunger relative to the barrel and, consequently,'a predetermined quantity of liquid is adapted to be withdrawn into the tip and dispensed therefrom.

11. The invention in-accordance with claim' 9 wherein said plunger includes indicia means for setting the'plunger relative to the barrelin selecting a predetermined dosage of liquid to be dispensed.

12. An automatis pipette comprising a barrel, a plunger reciprocal forwardly and rearwardly therein, meansfor coupling a pipette tip to said barrel such that upon .retraction rearwardly of said piston relative to said barrel, liquid is adapted into said tip and upon forward movement of the piston the liquid is adapted to be'di'spensed from the tip, a handle extending laterally from the barrel and adapted to be grasped to facilitate manipulation of the pipette and reciprocation of the plunger, said coupling means being so constructed and arranged suchthat the longitudinal axis of said tip is disposed at an acute angle with respect to. the axis of said barrel, and key means being provided by surfaces of said coupling means and the forward end of said barrel for assuring a predetermined disposition of the coupling means relative to said barrel.

13. The invention in accordance with claim 12 wherein switch means are coupled with said plunger and adapted to be actuated by the reciprocation thereof whereby a signal is adapted to be generated when saidplungers'assumes a predetermined position relative to the barrel at which a predetermined dosage of liquid is dispensed from the tip.

14. The invention in accordance with claim 13 wherein electrical jack connection means is also disposed in said handle for receiving an electrical jack adapted to transmit the signal generated upon closing of the switch means.

15. An automatic pipette comprising a barrel, a plunger reciprocal forwardly and rearwardly therein, meansfor coupling a pipette tip to said barrel such that upon retraction rearwardly-of said piston relative to said barrel, liquid is adapted into said tip andupon forward movement of the piston liquid is adapted to be dispensed from the tip, a handle extending laterally from the barreland adapted to be grasped to facilitate manipulation of the pipette and reciprocation of the plunger, switch means being coupled with said plunger and adapted to be actuated by the reciprocation thereof whereby a signal is adapted to be generated when said plunger assumes a predetermined position relative to the barrel at which a predetermined dosage of liquid is dispensed from the tip, and a safety switch being located in the handle and coupled with said switch means for opening the circuit to the switch means prior to actual dispensing of the liquid in the tip and upon closing of the switch, the switch means being adapted to be actuated upon dispensing of the tip contents.

16. The invention in accordance with claim wherein said dosage regulating means including projecting stop and guide flanges on the interior of said barrel and a laterally extending flange on interior surfaces of said plunger whereby upon predetermined rotation of said plunger when fully withdrawn relative to the barrel said lateral flange is adapted to be guided by the guide flanges during the reciprocal movement of the plunger relative to the barrel and have its movement limited by a stop flange to thereby impart a predetermined stroke to the plunger relative to the barrel and, consequently, a predetermined quantity of liquid is adapted to be withdrawn into the tip and dispensed therefrom.

17. The invention in accordance with claim 16 wherein said plunger includes indicia means for setting the plunger relative to the barrel in selecting a predetermined dosage of liquid to be dispensed.

18. A disposable pipette tip formed from an essentially clear resinous material comprising an elongated tube having an elongated axis and having an integral coaxial hub at one end and an integral coaxial externally and uniformly tapered dispensing end, the hub end having means for coupling the pipette tip to a pipette, said tip having integral coaxial means for manually gripping the exterior of the tip adjacent the hub end to facilitate coupling the tip to a pipette, the taper of the dispensing end defining a knife edge, the inner wall of the tip being slightly and uniformly tapered from the dispensing end to the hub end for substantially the entire length of the tube such that at a distance from about slightly less than 2.5 inches from the dispensing end, the inner wall being larger at the hub end than at the dispensing end, the envelope defined by the inner wall of the tip possesses a capacity of about slightly more than .2 ml.

19. A disposable pipette tip formed from an essentially clear resinous material comprising an elongated tube of substantially uniform thickness over a substantial portion of its length, said tube having an elongated axis and having an integral coaxial hub at one end and an integral coaxial externally and uniformly tapered dispensing end, said hub having integral coaxial means for coupling the tip to a pipette, said tip having integral coaxial means adjacent the hub end for manually gripping the external surfaces of the tip to facilitate the coupling of the tip to a pipette, said tapered end defining a knife edge at the dispensing end of the tip, said tapered end being at an angle of approximately 30 with the longitudinal axis of the tube, the inner wall of the tip being slightly and uniformly tapered from the tapered end to the hub end in a ratio not less than 1:3, the inner wall being larger at the hub end than at the dispensing end, and at a distance of about slightly less than 2.5 inches from the tapered end of said tip having a capacity of about slightly more than .2 ml.

20. The invention in accordance with claim 19 wherein the means for coupling the tip to a pipette at said hub end includes a frusto-conical external surface decreasing in diameter away from the tapered end, and the means for manually gripping the external surface of said tip includes rib means interposed between the tapered end and frusto-conical external surface for facilitating the coupling of the hub with a pipette.

References Cited by the Examiner UNITED STATES PATENTS 1,039,591 9/1912 Prideaux.

2,161,711 6/1939 Kadavy 128234 2,566,436 9/1951 Waite 22276 X 2,959,170 11/1960 Laub 128-218 2,959,964 11/ 1960 Streitfield 73-425 .6 3,013,435 12/1961 Rodrigues 222309 X 3,040,931 6/1962 Sany.

3,084,592 4/ 1963 Scott.

FOREIGN PATENTS 711,644 6/ 1931 France.

LOUIS R. PRINCE, Primary Examiner.

S. C. SWISHER, Assistant Examiner. 

1. AN AUTOMATIC PIPETTE COMPRISING A BARREL, A PISTON RECIPROCAL FORWARDLY AND REARWARDLY THEREIN, A DISPOSABLE TIP, COUPLING MEANS FOR INTERCONNECTING SAID TIP WITH THE FORWARD END OF SAID BARREL, WHEREBY UPON RETRACTION REARWARDLY OF SAID PISTON RELATIVE TO SAID BARREL, LIQUID IS ADAPTED TO BE DRAWN INTO SAID TIP SHORT OF SAID BARREL WITH A BODY OF AIR BEING DISPOSED INTERMEDIATE THE PISTON AND THE LIQUID IN SAID TIP AND UPON FORWARD MOVEMENT OF THE PISTON, THE INTERPOSED AIR WILL ACT ON THE LIQUID TO DISPENSE THE LIQUID FROM THE TIP, SAID COUPLING MEANS BEING SO CONSTRUCTED AND ARRANGED SUCH THAT THE LONGITUDINAL AXIS OF SAID TIP IS DISPOSED AT AN ACUTE ANGLE WITH RESPECT TO THE AXIS OF SAID BARREL, AND KEY MEANS PROVIDED BY SURFACES OF SAID COUPLING MEANS AND THE FORWARD END OF SAID BARREL FOR ASSURING A PREDETERMINED DISPOSITION OF THE COUPLING MEANS RELATIVE TO SAID BARREL. 